Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer

Karousou, Evgenia; Misra, Suniti; Ghatak, Shibnath; Dobra, Katalin; Götte, Martin; Vigetti, Davide; Passi, Alberto; Karamanos, Nikos K.; Skandalis, Spyros S.

doi:10.1016/j.matbio.2016.10.001

Cited by 166 publications

(161 citation statements)

References 211 publications

(179 reference statements)

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“…CAFs not only utilize HA in order to migrate close to the tumor cells but their autocrine production of HA also stimulates the migration of the HA-binding tumor subpopulation [181]. The reduction in HA synthesis and the downregulation of the major HA synthase, HAS2, have been proved useful for the inhibition of cancer progression [39,41,[183][184][185][186][187][188][189].…”

Section: Biological Importance Of Ha Fractions In Cancermentioning

confidence: 99%

Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer

et al. 2019

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Hyaluronan (HA) is a linear nonsulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High‐molecular weight HA exhibits different biological properties than oligomers and low‐molecular weight HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action. This phenomenon is attributed to the different manner of interaction with the HA receptors, especially CD44 and RHAMM. Both receptors can trigger signaling cascades that regulate cell functional properties, such as proliferation migration, angiogenesis, and wound healing. HA fragments are able to enhance or attenuate the HA receptor‐mediated signaling pathways, as they compete with the endogenous HA for binding to the receptors. The modulation of these pathways could be crucial for the development of pathological conditions, such as inflammation and cancer. The primary goal of this review is to critically present the importance of HA molecular size on cellular signaling, functional cell properties, and morphology in normal and pathological conditions, including inflammation and cancer. A deeper understanding of these mechanisms could contribute to the development of novel therapeutic strategies.

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Section: Biological Importance Of Ha Fractions In Cancermentioning

confidence: 99%

Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer

et al. 2019

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“…HA plays the following dual function: in normal ECM, providing tissue homeostasis, biomechanical integrity, and structure and assembly of tissues (Wight, ). In malignant tumors, HA is frequently increased and transmits signals to the cytoplasm; thereby, tumor cell proliferation, motility and invasion are increased (Karousou et al, ; Park et al, ). HA facilitates tumor growth by opening up spaces for the tumor to migrate and by interacting with HA‐binding molecules, and it assists tumor cell adhesion and migration (Sherman et al, ; Boregowda et al, ; Stuhlmeier, ).…”

Section: The Brain Extracellular Matrix and Its Interaction With Gliomentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

166

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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“…Importantly, neovascularization is a marker of atherosclerotic plaque destabilization. The hyaluronic acid and its receptor, CD44, generally promotes tumor progression . For example, it induces the aforementioned oncomir miR21 by activation of the c‐Jun signaling pathway .…”

Section: Extracellular Matrixmentioning

confidence: 96%

“…The hyaluronic acid and its receptor, CD44, generally promotes tumor progression. 47 For example, it induces the aforementioned oncomir miR21 by activation of the c-Jun signaling pathway. 48 Therefore, the role of hyaluronic acid in atherosclerotic plaque destabilization needs to be further clarified, as well as its regulation by microRNA molecules.…”

Section: Proteoglycansmentioning

confidence: 99%

MicroRNA regulation of extracellular matrix components in the process of atherosclerotic plaque destabilization

Kowara

Cudnoch‐Jędrzejewska

Opolski

et al. 2017

Clin Exp Pharma Physio

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SummaryThe process of atherosclerotic plaque destabilization, leading to myocardial infarction, is still not fully understood. The pathway -composed of structural and regulatory proteins of the extracellular matrix (ECM) such as collagen, elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and serine proteases -is one potential way of atherosclerotic plaque destabilization. The expression of these proteins is controlled by different microRNA molecules. The goal of this paper is to summarize the current investigations and knowledge about ECM in the process of atherosclerotic plaque destabilization, giving special attention to epigenetic expression regulation by microRNA. K E Y W O R D Satherosclerosis, collagen, extracellular matrix, metalloproteinases, RNA interference

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Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer

Cited by 166 publications

References 211 publications

Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer

Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer

Glioma infiltration and extracellular matrix: key players and modulators

MicroRNA regulation of extracellular matrix components in the process of atherosclerotic plaque destabilization

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